title: Interaction of glutathione peroxidase-1 and selenium in endemic dilated cardiomyopathy.
abstract: BACKGROUND
  Keshan disease (KD) is a fatal dilated cardiomyopathy with unknown etiology. We studied the gene-environment interaction in the pathogenesis of KD by assessing the association of low blood selenium and polymorphisms in glutathione peroxidase-1 (GPx-1) gene.
  
  
  METHODS
  The concentration of blood selenium and the activity and polymorphisms of GPx-1 in 71KD patients and 290 controls were measured. The functions of rat neonatal cardiomyocytes resulting from overexpression of 2 variants of GPx-1 were studied.
  
  
  RESULTS
  Blood concentration of selenium and GPx-1 activity were lower in patients than in controls. Genetic analysis revealed a single nucleotide polymorphism (Pro198Leu) in GPx-1 gene associated with selenium deficiency as well as impaired GPx-1 activity. Gene-environment interaction analysis revealed a synergistic-multiplicative interaction between polymorphism of GPx-1 and selenium deficiency. Overexpression of the GPx-1 leucine-containing allele in cultured cardiomyocytes caused a 30% reduction in selenium-induced GPx-1 activity and increased serum starvation induced apoptosis as compared with that of the wild-type variant 198Pro.
  
  
  CONCLUSIONS
  Selenium deficiency in carriers with the GPx-1 leucine-containing allele is associated with low GPx-1 enzyme activity, which may, in turn, increase the incidence of KD. Results from this unique disease may have broad implications for a gene-environment reaction in the etiology of other diseases.
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital, Key Laboratory of Environment and Genes Related to Diseases of Education Ministry, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Cong
authors.initials: C
authors.lastname: Lei
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Niu
authors.forename: Jin
authors.initials: J
authors.lastname: Wei
authors.forename: Jianhong
authors.initials: J
authors.lastname: Zhu
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhu
mesh_terms: D000368:Aged; D000483:Alleles; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000502:physiology; D001483:Base Sequence; D002311:Cardiomyopathy, Dilated / Q000097:blood* / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D002478:Cells, Cultured; D004796:Clinical Enzyme Tests; D005838:Genotype; D005979:Glutathione Peroxidase / Q000097:blood* / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007930:Leucine / Q000235:genetics; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D011110:Polymorphism, Genetic; D051381:Rats; D012643:Selenium / Q000097:blood* / Q000172:deficiency*; D000094765:Glutathione Peroxidase GPX1
chemical_list: D005979:Glutathione Peroxidase; D007930:Leucine; D012643:Selenium; D000094765:Glutathione Peroxidase GPX1